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Thyroid presentation
Neoplastic and Non-neoplastic Rodent Thyroid Lesions and Their RelevanceBob MaronpotRTP Rodent Pathology Course - 2014
AcknowledgmentThe majority of the photomicrographs in this presentation were provided courtesy of the National Toxicology Program Archives
http://ntp.niehs.nih.gov/nnl/
Toxicologic Pathology Vol 22 (2): 179-186, 1994Haschek and Rousseauxs Handbook of Toxicologic Pathology, 3rd Edition (2013)
HypothalamusPit
TRH
ThyroidTSH
BloodT3T4T3/T4Negative feedback
Liver
Elimination
T4
T3
TSH
Basics of Thyroid Hormone PhysiologyFigure courtesy of Doug Wolf
55
Rat-Human Species Differences
Effects of Xenobiotics on the Thyroid
Toxicologic Pathology Vol 22 (2): 179-186, 1994
Effects of Xenobiotics on the Thyroid
Toxicologic Pathology Vol 22 (2): 179-186, 1994
NomenclatureThyroid changes affecting the thyroid in general (e.g., inflammation)Follicles changes restricted to the follicles (e.g., secretory depletion)Follicular epithelium - effect is specific to the follicular epithelium (e.g., hypertrophy)C-Cells changes specifically affecting the C-cells (e.g., hyperplasia)
Thyroid LesionsNon-ProliferativeCystsEnlarged/dilated folliclesSecretory depletion/colloid depletionColloid alterationDegenerationInflammationMineralizationHypertrophy
ProliferativeFollicular epitheliumHyperplasiaGeneralizedCysticAdenomaAdenocarcinomaC-cellsHyperplasiaDiffuseFocalAdenomaCarcinoma
Parathyroid LesionsNon-ProliferativeCystsSyncytial giant cells/cytomegalyAngiectasisProliferativeHyperplasiaAdenomaCarcinoma
Rat Thyroid - Normal
A49050 Vehicle male F344 Cresol Normal. C-cells normal13
Rat Thyroid - Normal
A50388 Subchronic F344 Normal14
Rat Thyroid - Normal
A49766 Subchronic Vehicle male F344 Normal15
Rat Thyroid - Normal
A49051 Cresol Vehicle male F344 Normal16
Mouse Thyroid - Normal
A45151 Female normal FVB/N17
Rat Thyroid - Normal
A47139 Ginko F344 control Normal18
Mouse Thyroid - Normal
A40629 mouse B6C3F1 Untreated male Normal19
Rat versus Mouse
Rat Thyroid - Mineral
A40749 methyjlimidazole F344 dx= follicular cell hyperplasia and mineral21
Embryonal Cyst
A08337 Aminonotrophenol F344 dx= cystic duct22
Embryonal Cyst
A05288 Vehicle female F344 dx=23
Embryonal Cyst
A24178 p-Nitroaniline B6C3F1 dx= thyroglossal cyst24
Embryonal Cyst
A24180 p-Nitroaniline B6C3F1 dx= thyroglossal cyst
25
Ectopic Thymus
A12939 B6C3F1 Ectopic thymus26
Thyroid LesionsNon-ProliferativeCystsEnlarged/dilated folliclesSecretory depletion/colloid depletionColloid alterationDegenerationInflammationMineralizationHypertrophy
ProliferativeFollicular epitheliumHyperplasiaGeneralizedCysticAdenomaAdenocarcinomaC-cellsHyperplasiaDiffuseFocalAdenomaCarcinoma
Enlarged Follicles
F344
A05294 4-vinylcyclohexane F344 dx= enlarged follicles28
Follicular Degeneration
A51381 Milk thistle extract B6C3F1 follicular degeneration29
Follicular Degeneration
B6C3F1 Control Female
A48961 B6C3F1 control female Follicular degeneration 30
Follicular Degeneration
degeneration31
Follicular Degeneration
Ciliated Vehicle female32
Pigment
Vehicle control. Male F344
A07951 pigment Vehicle Male F34433
Pigment
High dose methoxypsoralen male F344
A07961 Pigment Methoxypsoralen High dose male F34434
Pigment
1 of 3
A10435 pigment Trinitrofluorenone F344 minocycline semisynthetic tetracycline derivative; dark brown resembles melanin35
Pigment
2 of 3
A10436 pigment Trinitrofluorenone F344minocycline semisynthetic tetracycline derivative; dark brown resembles melanin36
Pigment
3 of 3Subchronic trinitrofluorenone study in F344 rats
A10437 pigment Trinitrofluorenone F344 minocycline semisynthetic tetracycline derivative; dark brown resembles melanin
37
Follicular Cell Hypertrophy
A40643 B6C3F1 control male dx=hypertrophy 2-methylimidazole38
Concurrent Control
A40629 to cf to A40643 2-methylimidazole normal B6C3F1 control male39
Follicular Cell Hypertrophy
1 of 3Female SD Rat
A52749 PCB 118 SD Female TEF 2 yr gavage dx= hypertrophy41
Follicular Cell Hypertrophy
2 of 3
A52750 PCB 118 SD Female TEF 2 yr gavage dx= hypertrophy42
Follicular Cell Hypertrophy
3 of 3
A52751 PCB 118 SD Female TEF 2 yr gavage dx= hypertrophy43
Follicular Cell Hypertrophy
Subchronic study. SD Rat
A47461 PCN subchronic dx = hypertrophy Sprague Dawley Female
44
Hypertrophy
Subchronic study. F344 Rat
A49763 Tetrachlorobenzene Subchronic dx=hypertrophy F34445
Hypertrophy
Harlan SD Rat.
A66377 Harlan SD Indole-3-carbinol Marked follicular cell hypertrophy46
Hypertrophy & Hyperplasia
1 of 4Subchronic study. F344 Rat
A49772 Pentachlorobenzene Subchronic dx = hypertrophy Some hyperplasia present F344 47
Hypertrophy & Hyperplasia
2 of 4
A49773 Pentachlorobenzene Subchronic dx = hypertrophy Some hyperplasia present F344 48
Hypertrophy & Hyperplasia
3 of 4
A4977449
Hypertrophy & Hyperplasia
4 of 4
A49776 Pentachlorobenzene Subchronic dx = hypertrophy Some hyperplasia present F344 50
Hypertrophy
A44355 dx follicular cell hypertrophy PCB mixture Female SD 2 yr gavage51
Hypertrophy
A40345 dx follicle atrophy?? Really is hypertrophy dioxin mixture Female SD 2 yr gavage52
Secretory Depletion
Subchronic study. F344 Rat
A50379 Pentabromophenyloxide Subchronic Fischer 344 dx secretory depletion Flame retardant. Still under study and no pathology findings yet available on NTP web site. 53
Secretory Depletion
1 of 2Subchronic study. F344 Rat
A50373 Pentabromophenyloxide Subchronic Fischer 344 dx secretory depletion Flame retardant. Still under study and no pathology findings yet available on NTP web site. 54
Secretory Depletion
2 of 2Subchronic study. F344 Rat
A50380 Pentabromophenyloxide Subchronic Fischer 344 dx secretory depletion Flame retardant. Still under study and no pathology findings yet available on NTP web site. 55
Secretory Depletion
Chronic study. F344 Rat
A11171 secretory depletion F344 CI Acid Red 11456
Lymphoid Infiltrate, Secretory Depletion and Hypertrophy
1 of 2Subchronic study. FVB/N Mouse.
A45156 Sodium bromate subchronic study in FVB/N mouse Lymphoid infiltrate, secretory depletion, follicular cell hypertrophy57
Lymphoid Infiltrate, Secretory Depletion and Hypertrophy
2 of 2
A45157 Sodium bromate subchronic study in FVB/N mouse Lymphoid infiltrate, secretory depletion, follicular cell hypertrophy58
Lymphoid Infiltrate, Secretory Depletion and Hypertrophy
1 of 2Female SD Rat
A51536 A51537 Tetrachloroazobenzene Female SD Inflammation and hypertrophy
59
Lymphoid Infiltrate, Secretory Depletion, Pigment, and Hypertrophy
2 of 2
A51537 Tetrachloroazobenzene Female SD Inflammation and hypertrophy
60
Periarteritis
1 of 2B6C3F1 Mouse
A23377 B6C3F1 Mouse tetrafluoroethylene chronic dx=periarteritis 61
Periarteritis
2 of 2
A23378 B6C3F1 Mouse tetrafluoroethylene chronic dx=periarteritis 62
Thyroid LesionsNon-ProliferativeCystsEnlarged/dilated folliclesSecretory depletion/colloid depletionColloid alterationDegenerationInflammationMineralizationHypertrophy
ProliferativeFollicular epitheliumHyperplasiaGeneralizedCysticAdenomaAdenocarcinomaC-cellsHyperplasiaDiffuseFocalAdenomaCarcinoma
Take away 1. Hypertrophy often with hyperplasia. 2. Concurrent control 3. dx the primary change63
Follicular Cell Proliferative LesionsHyperplasiaFollicular cell hyperplasiaDiffuseFocal (simple papillary infoldings)Cystic hyperplasiaMinimal compressionAdenomaCircumscribed, compressiveGrowth pattern complex papillary or follicularCells well differentiated and hyperchromaticCarcinomaCapsular invasionInfiltrative, disorganized, varied growth patternCellular pleomorphism and atypiaVarying sized folliclesScirrhous reaction
Usually unilateral64
Diffuse Hyperplasia
1 of 2F344 Rat Chronic Study
A08048 F344 Mercaptobenzimidazole Chronic study65
Diffuse Hyperplasia
2 of 2
A8049 F344 Mercaptobenzimidazole Chronic study
66
Focal Hyperplasia
B6C3F1 Mouse Sodium Chlorate Study
A40905 B6C3F1 Sodium chlorate dx= follicular cell hyperplasia67
Follicular Cell Hyperplasia
1 of 2B6C3F1 Mouse
A40646 2-methylimidazole B6C3F1 dx= hyperplasia and hypertrophy?68
Follicular Cell Hyperplasia
2 of 2
A40647 2-methylimidazole B6C3F1 dx= hyperplasia and hypertrophy?69
Hyperplasia vs. Adenoma
1 of 2B6C3F1 Mouse. Original dx = Adenoma
A57552 ginkgo biloba extract B6C3F1 dx= adenoma70
Hyperplasia vs. Adenoma
2 of 2
A57553 ginkgo biloba extract B6C3F1 dx= adenoma
71
Hyperplasia vs. Adenoma
1 of 2B6C3F1 Mouse Original dx = Hyperplasia
A43866 Methylisobutylketone B6C3F1 dx=hyperplasia72
Hyperplasia vs. Adenoma
2 of 2
A4386773
Follicular Cell Adenoma
F344 Rat
A09478 Tris chloroethylphosphate F344 dx follicular cell adenoma74
Cystic Follicular Cell Adenoma
A03709 F344 75
Follicular Cell Adenoma
F344 Rat
A57079 ginko biloba extract F344 dx=adenoma76
Follicular Cell Adenoma
1 of 4F344 Rat
A54750 Kava kava Follicular adenoma F34477
Follicular Cell Adenoma
2 of 4
A5475178
Follicular Cell Adenoma
3 of 4
A5475279
Follicular Cell Adenoma
4 of 4
A54753 Kavakava Follicular adenoma
80
Follicular Cell Adenoma
1 of 3SD Female Rat
A44360 PCB SD Follicular adenoma81
Follicular Cell Adenoma
2 of 3
A4436182
Follicular Cell Adenoma
3 of 3
A4436283
Follicular Cell Carcinoma
1 of 2Wistar Han Rat
P3273459 Han Wistar Follicular Carcinoma
84
Follicular Cell Carcinoma
2 of 2
P3273461 Han Wistar Follicular Carcinoma
85
Follicular Cell Carcinoma
B6C3F1 Mouse
A24203 methyl bromide B6C3F1 control female dx= carcinoma and follicular degeneration86
Follicular Cell Carcinoma
F344 Rat
A29499 Isobutene F344 dx= follicular cell CA87
Follicular Cell Carcinoma
A30974 Isobutene F344 dx=carcinoma, invasion88
Follicular Cell Carcinoma
1 of 2F344 Rat
A46141 Methylene blue trihydrate F344 Follicular cell CA89
Follicular Cell Carcinoma
2 of 2
A46143 Methylene blue trihydrate F344 Follicular cell CA90
Macrofollicular Carcinoma
A0553691
Squamous Cell Carcinoma
1 of 2F344 Rat
A07405 Dibromopropanol SCC F34492
Squamous Cell Carcinoma
2 of 2
A4740693
Follicular Cell Proliferative LesionsHyperplasiaFollicular cell hyperplasiaDiffuseFocal (simple papillary infoldings)Cystic hyperplasiaMinimal compressionAdenomaCircumscribed, compressiveGrowth pattern complex papillary or follicularCells well differentiated and hyperchromaticCarcinomaCapsular invasionInfiltrative, disorganized, varied growth patternCellular pleomorphism and atypiaVarying sized folliclesScirrhous reaction
Usually unilateral94
C-Cell Proliferative LesionsHyperplasiaDiffuse, focal, bothMaximum diameter less than 5 average colloid-filled folliclesAdenomaMaximum diameter greater than 5 average colloid-filled folliclesDiscrete, circumscribedMay compress adjacent folliclesCarcinomaInfiltrative, local & capsular invasionPleomorphism & atypia may be present
Usually unilateral95
C-Cell Hyperplasia, Diffuse
1 of 2
A42474 F344 2-methylimidazole dx= c-cell hyperplasia, diffuse
96
C-Cell Hyperplasia, Diffuse
2 of 2
A42475 F344 2-methylimidazole dx= c-cell hyperplasia, diffuse
97
C-Cell Hyperplasia, Focal
1 of 2
A42478 F344 2-methylimidazole dx= c-cell hyperplasia, focal98
C-Cell Hyperplasia, Focal
2 of 2
A42482 F344 2-methylimidazole dx= c-cell hyperplasia, focal99
C Cell Hyperplasia
Female SD Rat
A45816 Female SD rat, vehicle control dx= c-cell hyperplasia100
Hyperplasia vs Adenoma
1 of 2F344 Rat
A42486 F344 Untreated female dx=c-cell adenoma101
2 of 2Original dx = Adenoma
A42488 F344 Untreated female dx=c-cell adenoma102
C-Cell Adenoma
A10075 F344 Trichlorfon dx=c-cell adenoma103
C-cell Adenoma
A05541 Nalidixic Acid F344 dx= c-cell tumor with amyloid104
C-Cell Carcinoma
1 of 3F344 Rat
A46215 F344 Methylene blue trihydrate dx=C-cell carcinoma105
C-Cell Carcinoma
2 of 3
A46216 F344 Methylene blue trihydrate dx=C-cell carcinoma
106
C-Cell Carcinoma
3 of 3
A46217 F344 Methylene blue trihydrate dx=C-cell carcinoma
107
C-Cell Carcinoma
1 of 3
A47948 Formamide F344 dx=c-cell carcinoma108
C-Cell Carcinoma
2 of 3
A47949 Formamide F344 dx=c-cell carcinoma109
C-Cell Carcinoma
3 of 3
A47950 Formamide F344 dx=c-cell carcinoma110
C-Cell Proliferative LesionsHyperplasiaDiffuse, focal, bothMaximum diameter less than 5 average colloid-filled folliclesAdenomaMaximum diameter greater than 5 average colloid-filled folliclesDiscrete, circumscribedMay compress adjacent folliclesCarcinomaInfiltrative, local & capsular invasionPleomorphism & atypia may be present
Usually unilateral111
If I have more time..
112
Parathyroid LesionsNon-ProliferativeCystsSyncytial giant cells/cytomegalyAngiectasisProliferativeHyperplasiaAdenomaCarcinoma
Normal Parathyroid
A54698 KavaKava Extract F344 Normal114
Cyst, NOS
A05286 Phenol F344 dx= cyst, NOS115
Embryonal Cyst
1 of 2
A23383 Aminodibromoanthraquinone B6C3F1 dx=thyroglossal duct cyst116
Embryonal Cyst
2 of 2
A23385 Aminodibromoanthraquinone B6C3F1 dx=thyroglossal duct cyst
117
Ectopic Thymus & Embryonal Cyst
1 of 2
A59824 BALB/c adenoviral vector subchronic study dx - = cyst, ectopic thymus118
Embryonal Cyst
2 of 2
A59825 BALB/c adenoviral vector subchronic study dx - = cyst119
Angiectasis
1 of 2
A49628 Mouse (MW)_ Viral vector, subchronic dx= angiectasis120
Angiectasis
2 of 2
A49629 Mouse (MW)_ Viral vector, subchronic dx= angiectasis121
Cytomegaly
A05290 Propylene oxide F344 dx= cyjtomegaly122
Syncytial Giant Cells
A06101 F344 rat dx= syncytial giant cells123
Parathyroid Fibrosis
Downloaded from NTP Non-Neoplastic Lesion Atlas 1 of 2
A28149 Chloroprene F344 dx=fibrosis124
Parathyroid Fibrosis
Downloaded from NTP Non-Neoplastic Lesion Atlas 2 of 2
A28151 Chloroprene F344 dx=fibrosis
125
Ectopic Thymus
A26251 B6C3F1 Subchronic Ectopic thymus126
Parathyroid LesionsNon-ProliferativeCystsSyncytial giant cells/cytomegalyAngiectasisProliferativeHyperplasiaAdenomaCarcinoma
Parathyroid Hyperplasia, Diffuse
1 of 3
A03511 F344 Asbestos study dx= diffuse hyperplasia128
Parathyroid Hyperplasia, Diffuse
2 of 3
A03513 F344 Asbestos study dx= diffuse hyperplasia & C-cell proliferative lesion (dx=adenoma)
129
Parathyroid Hyperplasia
3 of 3
A03514 F344 Asbestos study dx= diffuse hyperplasia & C-cell proliferative lesion (dx=adenoma)130
Parathyroid Hyperplasia
A02622 naphthyl ethyldiamine F344 dx- focal hyperplasia131
Parathyroid Hyperplasia
1 of 2
Parathyroid Hyperplasia
2 of 2
A54695133
Parathyroid Adenoma
1 of 2
A14777 F344 Benzylchlorophenol dx= adenoma134
Parathyroid Adenoma
2 of 2
A14778 F344 Benzylchlorophenol dx= adenoma
135
Parathyroid Adenoma
1 of 2
A22217 F344 Vehicle male Nickel subsulfide dx= adenoma136
Parathyroid Adenoma
2 of 2
A22218 F344 Vehicle male Nickel subsulfide dx= adenoma
137
Parathyroid Adenoma
1 of 2
A02310n Rotenone F344 dx=adenoma138
Parathyroid Adenoma
2 of 2
A02311 Rotenone F344 dx=adenoma
139
Parathyroid Carcinoma
1 of 2
A05300 Telone II F344 dx= carcinoma140
Parathyroid Carcinoma
2 of 2
A05301 Telone II F344 dx= carcinoma
141
Thank you for your attention
142
ParameterHumanRat
Thyroxine-binding globulinPresentEssentially absent
T4 Half-life5-9 days0.5-1 days
T3 Half-life1 day0.25 days
T4 production rate/kg BW1X10 x that in humans
TSH1X6-60 x that in humans
Follicular morphologyLow cuboidalCuboidal
Sex differences
Serum TSHSexes equalM 2 x F
Cancer sensitivityF = 2.5 x MM>F